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      Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

      research-article
      103 , 217 , 218 , 19 , 79 , 112 , 288 , 97 , 70 , 265 , 257 , 318 , 131 , 15 , 158 , 254 , 301 , 195 , 353 , 143 , 321 , 354 , 131 , 357 , 350 , 165 , 260 , 179 , 39 , 111 , 283 , 282 , 277 , 119 , 260 , 58 , 106 , 72 , 73 , 250 , 254 , 100 , 261 , 140 , 92 , 169 , 82 , 144 , 258 , 174 , 221 , 238 , 78 , 134 , 142 , 155 , 379 , 136 , 334 , 305 , 128 , 180 , 337 , 148 , 283 , 212 , 360 , 160 , 201 , 330 , 359 , 181 , 131 , 279 , 170 , 171 , 172 , 133 , 131 , 25 , 23 , 239 , 23 , 220 , 222 , 373 , 346 , 340 , 7 , 227 , 308 , 352 , 335 , 141 , 218 , 116 , 225 , 22 , 75 , 101 , 104 , 117 , 256 , 262 , 377 , 12 , 22 , 74 , 75 , 25 , 49 , 315 , 243 , 234 , 333 , 298 , 338 , 369 , 53 , 150 , 152 , 120 , 306 , 51 , 127 , 58 , 366 , 32 , 94 , 351 , 233 , 362 , 302 , 201 , 58 , 68 , 267 , 86 , 87 , 197 , 126 , 72 , 251 , 264 , 85 , 99 , 259 , 187 , 266 , 260 , 183 , 315 , 339 , 51 , 123 , 266 , 16 , 204 , 131 , 270 , 271 , 115 , 135 , 362 , 2 , 4 , 325 , 281 , 201 , 22 , 75 , 131 , 200 , 293 , 6 , 95 , 159 , 263 , 83 , 334 , 162 , 217 , 61 , 229 , 26 , 18 , 313 , 118 , 69 , 227 , 38 , 304 , 324 , 145 , 47 , 131 , 322 , 166 , 30 , 355 , 34 , 71 , 358 , 219 , 167 , 164 , 365 , 327 , 331 , 201 , 45 , 56 , 325 , 178 , 130 , 188 , 363 , 43 , 381 , 382 , 66 , 196 , 280 , 201 , 320 , 273 , 90 , 28 , 90 , 156 , 84 , 59 , 33 , 300 , 232 , 367 , 308 , 294 , 103 , 14 , 97 , 50 , 62 , 57 , 317 , 295 , 285 , 334 , 297 , 202 , 90 , 156 , 107 , 132 , 270 , 271 , 177 , 256 , 370 , 202 , 308 , 210 , 235 , 100 , 261 , 81 , 157 , 121 , 371 , 372 , 149 , 252 , 253 , 249 , 25 , 47 , 103 , 97 , 1 , 103 , 131 , 309 , 356 , 203 , 361 , 60 , 223 , 276 , 377 , 63 , 189 , 3 , 52 , 166 , 48 , 161 , 255 , 342 , 366 , 212 , 217 , 210 , 20 ,   309 , 67 , 154 , 5 , 205 , 345 , 7 , 247 , 200 , 369 , 168 , 235 , 316 , 190 , 163 , 153 , 93 , 206 , 242 , 76 , 13 , 209 , 303 , 286 , 187 , 11 , 207 , 114 , 212 , 224 , 191 , 181 , 42 , 44 , 184 , 185 , 186 , 131 , 217 , 37 , 296 , 375 , 231 , 39 , 283 , 41 , 296 , 343 , 151 , 153 , 110 , 245 , 102 , 326 , 380 , 272 , 332 , 167 , 36 , 53 , 182 , 183 , 208 , 319 , 137 , 199 , 383 , 10 , 91 , 8 , 299 , 35 , 175 , 213 , 275 , 362 , 364 , 217 , 284 , 61 , 289 , 291 , 292 , 14 , 195 , 307 , 308 , 194 , 214 , 21 , 311 , 312 , 96 , 348 , 349 , 138 , 122 , 193 , 201 , 189 , 228 , 120 , 378 , 369 , 80 , 139 , 55 , 278 , 88 , 327 , 328 , 329 , 323 , 65 , 198 , 131 , 103 , 173 , 98 , 240 , 105 , 244 , 17 , 344 , 275 , 274 , 369 , 22 , 75 , 369 , 215 , 27 , 46 , 146 , 113 , 347 , 348 , 314 , 248 , 216 , 226 , 237 , 27 , 176 , 192 , 336 , 128 , 180 , 337 , 201 , 201 , 310 , 24 , 269 , 369 , 374 , 23 , 40 , 368 , 230 , 166 , 268 , 125 , 201 , 270 , 271 , 31 , 89 , 147 , 64 , 246 , 16 , 204 , 384 , 29 , 241 , 236 , 211 , 341 , 108 , 109 , 290 , 376 , 77 , 217 , 162 , 326 , 124 , 9 , 129 , 287 , 54 , 119
      Journal of Extracellular Vesicles
      Taylor & Francis
      extracellular vesicles, exosomes, ectosomes, microvesicles, minimal information requirements, guidelines, standardization, microparticles, rigor, reproducibility

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          ABSTRACT

          The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

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          Most cited references193

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          Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells.

          Myeloid-derived suppressor cells (MDSCs) have been identified in humans and mice as a population of immature myeloid cells with the ability to suppress T cell activation. They accumulate in tumor-bearing mice and humans and have been shown to contribute to cancer development. Here, we have isolated tumor-derived exosomes (TDEs) from mouse cell lines and shown that an interaction between TDE-associated Hsp72 and MDSCs determines the suppressive activity of the MDSCs via activation of Stat3. In addition, tumor-derived soluble factors triggered MDSC expansion via activation of Erk. TDE-associated Hsp72 triggered Stat3 activation in MDSCs in a TLR2/MyD88-dependent manner through autocrine production of IL-6. Importantly, decreasing exosome production using dimethyl amiloride enhanced the in vivo antitumor efficacy of the chemotherapeutic drug cyclophosphamide in 3 different mouse tumor models. We also demonstrated that this mechanism is relevant in cancer patients, as TDEs from a human tumor cell line activated human MDSCs and triggered their suppressive function in an Hsp72/TLR2-dependent manner. Further, MDSCs from cancer patients treated with amiloride, a drug used to treat high blood pressure that also inhibits exosome formation, exhibited reduced suppressor functions. Collectively, our findings show in both mice and humans that Hsp72 expressed at the surface of TDEs restrains tumor immune surveillance by promoting MDSC suppressive functions.
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            Vesiclepedia: A Compendium for Extracellular Vesicles with Continuous Community Annotation

            Introduction A growing body of research has implicated extracellular vesicles (EVs), membraneous sacs released by a variety of cells, in diverse physiological and patho-physiological conditions [1]–[9]. They can be detected in body fluids including blood plasma, urine, saliva, amniotic fluid, breast milk, and pleural ascites [10]–[13], and contain proteins, lipids, and RNA representative of the host cell [14]–[18]. Though a definitive categorization is yet to be achieved [19], EVs can be broadly classified into three main classes, based on the mode of biogenesis: (i) ectosomes (also referred to as shedding microvesicles), (ii) exosomes, and (iii) apoptotic bodies (ABs) (see Box 1). Box 1. Categories of EVs Based on the Mode of Biogenesis Ectosomes or shedding microvesicles: Ectosomes are large EVs ranging between 50–1,000 nm in diameter [1]. They are shed from cells by outward protrusion (or budding) of a plasma membrane (PM) followed by fission of their membrane stalk [3],[5]. Ectosomes are released by a variety of cells including tumour cells, polymorphonuclear leucocytes, and aging erythrocytes [5]. The expression of phosphatidylserine (PS) on the membrane surface has been shown to be one of the characteristic features of ectosomes [1],[5]. Exosomes: Exosomes are small membranous vesicles of endocytic origin ranging from 40–100 nm in diameter [1],[42]. The density of exosomes varies from 1.10–1.21 g/ml and the commonly found markers of exosomes are Alix, TSG101, tetraspanins, and heat shock proteins [10]. The biogenesis of exosomes begins with the internalisation of molecules via endocytosis [42]. Once internalised, endocytosed molecules are either recycled to the PM or trafficked to multivesicular bodies (MVBs) [3]. The “exocytic” fate of MVBs results in their exocytic fusion with the PM, resulting in the release of intraluminal vesicles into the extracellular microenvironment as exosomes [43]. Apoptotic bodies: ABs are released from fragmented apoptotic cells and are 50–5,000 nm in diameter [1]. ABs are formed about during the process of programmed cell death or apoptosis, and represent the fragments of dying cells [3]. Similar to ectosomes, the expression of PS on the membrane surface has been shown to be a key characteristic of ABs [1],[5]. Recent studies have highlighted the role of EVs in intercellular communication [20]–[22], vaccine and drug delivery [23]–[25], and suggested a potential role in gene vector therapy [26] and as disease biomarkers [27]. More than three decades of research has advanced our basic understanding of these extracellular organelles and has generated large amounts of multidimensional data [14],[17]. Whilst most of the data are presented in the context of the biological findings/technical development and are mentioned in the inline text of the published article, a vast majority are often placed as supplementary information or not provided [28],[29]. Importantly, none of the molecular data in published articles is easily searchable [28]. With the immense interest in EVs and advances in high-throughput techniques, the data explosion will only increase. An online compendium of heterogeneous data will help the biomedical community to exploit the publicly available datasets and accelerate biological discovery [30]. ExoCarta and Need for an EV Database Existing databases are not comprehensive. For example, ExoCarta (http://www.exocarta.org), a database for molecular data (proteins, RNA, and lipids) identified in exosomes, catalogs only exosomal studies (as reported by the authors) [31]. Described initially in 2009 [32], the database has been visited by more than 16,000 unique users [33]. However, only exosomal studies (as reported by the authors) are catalogued in ExoCarta. With the confusion in terminologies and inefficiency of the purification protocols to clearly segregate each class of EVs [1],[19], it is critical to build a repository with data from all classes of EVs to understand more about the molecular repertoire of the various classes of EVs and their biological functions. This was the rationale for starting the Vesiclepedia online compendium for EVs. Vesiclepedia Vesiclepedia (http://www.microvesicles.org) is a manually curated compendium that contains molecular data identified in all classes of EVs, including AB, exosomes, large dense core vesicles, microparticles, and shedding microvesicles. The main criterion for manual curation was the presence of these vesicles in the extracellular microenvironment (EVs) as approved by the investigators who undertook the research. At this juncture, the EVs are named as per the curated article or submitting author, as the nomenclature is yet to be standardized [19]. Vesiclepedia was built using ZOPE, an open source content management system. Python a portable, interpreted, object oriented programming language was used in the three-tier system to connect the web interface with a MySQL database. Users can query or browse through proteins, lipids, and RNA molecules identified in EVs. Selecting a gene of interest directs the user to a gene/molecule page with information on the gene, its external references to other primary databases, experiment description of the study that identified the molecule, gene ontology based annotations, protein-protein interactions, and a graphical display of such network with relevance to molecules identified in EVs. Gene ontology annotations of molecular functions, biological process, and subcellular localization were retrieved from Entrez Gene [34] and mapped onto the proteins/mRNA identified in EVs. Under the experiment description, the sample source including the tissue name or cell line name, EV isolation procedures, and floatation gradient density as reported in the study are provided to the users. EV proteins are mapped onto their protein physical interactors along with the protein interaction identification method and PubMed identifier. Protein-protein interaction data was obtained from HPRD [35],[36], BioGRID [37], and Human Proteinpedia [38]. Database Issues and Community Annotation Though biological databases are indispensable resources for effective scientific research, it has to be noted that more than 20% of the database links are non-existent after their initial publication [39]–[41]. More than 50% of the databases are never updated reducing their usability [39], primarily due to the lack of continuous funding to maintain and update these resources. At this juncture, funding for databases is largely non-existent in many parts of the world. To overcome funding-related limitations and to keep the database updated, it is essential to involve the scientific community in annotating the data. Community annotation will significantly ease the burden of the curators who maintain and update the databases. Whilst community annotation is the permanent solution to keep the database updated, it seldom happens without a clear and transparent mechanism. In addition, the system has to ensure continuous deposition of data and “not just once” uploads. It has to be noted that data annotation can be regulated at two levels: (i) principal investigators voluntarily contributing data and (ii) peer-reviewed journals mandating data deposition before publication. Currently available community annotation tools don't have a continuous data deposition arrangement with an investigator. Additionally, only few journals mandate the deposition of data to public repositories before acceptance of a manuscript. To this end, we have initiated a community annotation project through Vesiclepedia that involves members of the EV research community (53 laboratories from 20 countries: Table 1). 10.1371/journal.pbio.1001450.t001 Table 1 Vesiclepedia statistics. Statistics n EV studies 341 Protein entries 35,264 mRNA entries 18,718 miRNA entries 1,772 Lipid molecules 342 Participating laboratories 53 Countries 20 Community annotation via Vesiclepedia happens through the founding members who agree to the conditions listed in Box 2. All of the members are listed in the credits page (http://www.microvesicles.org/credits). Box 2. Conditions to Become a Member of Vesiclepedia Community Annotation 1, Agree to submit datasets pertaining to EVs to Vesiclepedia before or after publication on a continuous basis 2, When reviewing articles, mandate/request investigators to submit datasets on EVs to Vesiclepedia On the basis of the agreement of community participation, members will submit their data automatically to Vesiclepedia before or after publication (Figure 1). Non-members submitting their research findings for peer-review through international journals might find the Vesiclepedia members as referees who will request/mandate the authors to submit the data to Vesiclepedia. By instituting this mechanism the datasets will be continuously deposited to Vesiclepedia. However, a non-member can also be appointed as a referee in which case the data might not be submitted to Vesiclepedia. The Vesiclepedia-data capture team will work along with the researchers to make the data submission as easy as possible. Detailed information on the format of data required for submission is provided in the Vesiclepedia webpage (http://www.microvesicles.org/data_submission). Currently, Vesiclepedia comprises 35,264 protein, 18,718 mRNA, 1,772 miRNA, and 342 lipid entries (Table 1). All of these data were obtained from 341 independent studies that were published over the past several years. 10.1371/journal.pbio.1001450.g001 Figure 1 A schematic of Vesiclepedia community annotation. Based on the agreement of community participation, members will submit their data automatically to Vesiclepedia before and after publication. Non-members submitting their research findings for peer-review through international journals might find some of the Vesiclepedia members as referees who will request/mandate the authors to submit the data to Vesiclepedia. Alternatively, a non-member can also be appointed as a referee in which case the data might not be submitted to Vesiclepedia. A non-member can also submit data directly to Vesiclepedia. Conclusions and Future Directions ExoCarta will be active even after the release of Vesiclepedia and will become a primary resource for high-quality exosomal datasets. Data deposited to ExoCarta can also be accessed through Vesiclepedia; however, only high quality exosomal datasets deposited to Vesiclepedia can be accessed through ExoCarta. With the launch of Vesiclepedia, we expect to have an organised data deposition mechanism. We expect active participation from the EV research community, along with the addition of new members and numerous heterogeneous datasets. All datasets submitted by EV researchers will be listed in the credits page along with the investigator details.
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              Isolation of exosomes from whole blood by integrating acoustics and microfluidics

              We have developed a unique, integrated, on-chip technology that is capable of isolating exosomes or other types of extracellular vesicles, directly from undiluted whole-blood samples in an automated fashion. Automated exosome isolation enables biohazard containment, short processing time, reproducible results with little human intervention, and convenient integration with downstream exosome analysis units. Our method of integrating acoustics and microfluidics leads to the isolation of exosomes with high purity and yield. With its label-free, contact-free, and biocompatible nature, it offers the potential to preserve the structures, characteristics, and functions of isolated exosomes. This automated, point-of-care device can further help in advancing exosome-related biomedical research with potential applications in health monitoring, disease diagnostics, and therapeutics. Exosomes are nanoscale extracellular vesicles that play an important role in many biological processes, including intercellular communications, antigen presentation, and the transport of proteins, RNA, and other molecules. Recently there has been significant interest in exosome-related fundamental research, seeking new exosome-based biomarkers for health monitoring and disease diagnoses. Here, we report a separation method based on acoustofluidics (i.e., the integration of acoustics and microfluidics) to isolate exosomes directly from whole blood in a label-free and contact-free manner. This acoustofluidic platform consists of two modules: a microscale cell-removal module that first removes larger blood components, followed by extracellular vesicle subgroup separation in the exosome-isolation module. In the cell-removal module, we demonstrate the isolation of 110-nm particles from a mixture of micro- and nanosized particles with a yield greater than 99%. In the exosome-isolation module, we isolate exosomes from an extracellular vesicle mixture with a purity of 98.4%. Integrating the two acoustofluidic modules onto a single chip, we isolated exosomes from whole blood with a blood cell removal rate of over 99.999%. With its ability to perform rapid, biocompatible, label-free, contact-free, and continuous-flow exosome isolation, the integrated acoustofluidic device offers a unique approach to investigate the role of exosomes in the onset and progression of human diseases with potential applications in health monitoring, medical diagnosis, targeted drug delivery, and personalized medicine.
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                Author and article information

                Journal
                J Extracell Vesicles
                J Extracell Vesicles
                ZJEV
                zjev20
                Journal of Extracellular Vesicles
                Taylor & Francis
                2001-3078
                2018
                23 November 2018
                : 7
                : 1
                : 1535750
                Affiliations
                [1 ]A.C.Camargo Cancer Center , São Paulo, Brazil
                [2 ]Aalborg University Hospital, Department of Clinical Biochemistry , Aalborg, Denmark
                [3 ]Aalborg University Hospital, Department of Clinical Immunology , Aalborg, Denmark
                [4 ]Aalborg University, Clinical Institute , Aalborg, Denmark
                [5 ]Aarhus University, Department of Clinical Medicine , Aarhus, Denmark
                [6 ]Aberystwyth University, Institute of Biological, Environmental and Rural Sciences (IBERS) , Aberystwyth, United Kingdom
                [7 ]Academic Medical Centre of the University of Amsterdam, Department of Clinical Chemistry and Vesicle Observation Centre , Amsterdam, The Netherlands
                [8 ]Advanced Center for Chronic Diseases , Santiago, Chile
                [9 ]Aix-Marseille Université, Institut Paoli-Calmettes, INSERM U1068, CNRS UMR7258, Centre de Recherche en Cancérologie de Marseille , Marseille, France
                [10 ]American Red Cross, Scientific Affairs , Gaithersburg, MD, USA
                [11 ]Amsterdam University Medical Centers, Department of Pathology , Amsterdam, The Netherlands
                [12 ]Aston University, School of Life & Health Sciences , Birmingham, UK
                [13 ]AstraZeneca, Discovery Sciences, IMED Biotech Unit , Cambridge, UK
                [14 ]AstraZeneca, Discovery Sciences, IMED Biotech Unit , Gothenburg, Sweden
                [15 ]Atlantic Cancer Research Institute , Moncton, Canada
                [16 ]BC Cancer, Canada’s Michael Smith Genome Sciences Centre , Vancouver, Canada
                [17 ]Beth Israel Deaconess Medical Center , Boston, MA, USA
                [18 ]Boston University School of Medicine , Boston, MA, USA
                [19 ]Brigham and Women’s Hospital, Center for Interdisciplinary Cardiovascular Sciences , Boston, MA, USA
                [20 ]Brown University, Women and Infants Hospital , Providence, RI, USA
                [21 ]Cancer Institute of JFCR , Tokyo, Japan
                [22 ]Cancer Research Institute Ghent , Ghent, Belgium
                [23 ]Cardiff University, School of Medicine , Cardiff, UK
                [24 ]Case Western Reserve University, Department of Medicine , Cleveland, OH, USA
                [25 ]Cedars-Sinai Medical Center , Los Angeles, CA, USA
                [26 ]Cedars-Sinai Medical Center, Smidt Heart Institute , Los Angeles, CA, USA
                [27 ]Center for Psychiatry and Neuroscience, INSERM U894 , Paris, France
                [28 ]Central Research Laboratories, Sysmex Co ., Kobe, Japan
                [29 ]Centro de Biología Molecular Severo Ochoa, Instituto de Investigación Sanitaria la Princesa (IIS-IP) , Madrid, Spain
                [30 ]Children’s Hospital of Los Angeles , Los Angeles, CA, USA
                [31 ]Chinese Academy of Sciences, Wenzhou Institute of Biomaterials and Engineering , Wenzhou, China
                [32 ]CIC bioGUNE, CIBERehd, Exosomes Laboratory & Metabolomics Platform , Derio, Spain
                [33 ]Cincinnati Cancer Center , Cincinnati, OH, USA
                [34 ]City of Hope Comprehensive Cancer Center, Beckman Research Institute, Department of Molecular Medicine , Duarte, CA, USA
                [35 ]Clínica las Condes, Extracellular Vesicles in Personalized Medicine Group , Santiago, Chile
                [36 ]CNC , Coimbra, Portugal
                [37 ]CNR Institute of Neuroscience , Milan, Italy
                [38 ]Copenhagen Lupus and Vasculitis Clinic, Section 4242 - Rigshospitalet , Copenhagen, Denmark
                [39 ]CSGI - Research Center for Colloids and Nanoscience , Florence, Italy
                [40 ]Danube University Krems, Department for Biomedical Research and Christian Doppler Laboratory for Innovative Therapy Approaches in Sepsis , Krems an der Donau, Austria
                [41 ]Department of Veterans Affairs , San Francisco, CA, USA
                [42 ]Duke University Medical Center, Departments of Medicine and Immunology , Durham, NC, USA
                [43 ]Duke University, Department of Ophthalmology , Durham, NC, USA
                [44 ]Durham VAMC, Medical Research Service , Durham, NC, USA
                [45 ]École normale supérieure , Paris, France
                [46 ]Department of Pathology, Erasmus MC, Erasmus Optical Imaging Centre , Rotterdam, The Netherlands
                [47 ]Department of Urology , Rotterdam, The Netherlands
                [48 ]Erasmus MC , Rotterdam, The Netherlands
                [49 ]ETH Zurich, Institute of Pharmaceutical Sciences , Zurich, Switzerland
                [50 ]Eulji University, School of Medicine , Daejeon, South Korea
                [51 ]Evox Therapeutics Limited , Oxford, UK
                [52 ]EVSEARCH.DK , Denmark
                [53 ]Exogenus Therapeutics , Cantanhede, Portugal
                [54 ]Exosomics Siena SpA , Siena, Italy
                [55 ]FAU Erlangen-Nuremberg, Transfusion and Haemostaseology Department , Erlangen, Germany
                [56 ]Federal Research and Clinical Center of Physical-Chemical Medicine , Moscow, Russia
                [57 ]Federal University of Paraná, Department of Genetics, Human Molecular Genetics Laboratory , Curitiba, Brazil
                [58 ]FEMTO-ST Institute, UBFC, CNRS, ENSMM, UTBM , Besançon, France
                [59 ]Finnish Red Cross Blood Service, Research and Development , Helsinki, Finland
                [60 ]Florida State University College of Medicine, Department of Biomedical Sciences , Tallahassee, FL, USA
                [61 ]Fondazione IRCCS Istituto Nazionale dei Tumori, Unit of Immunotherapy of Human Tumors , Milan, Italy
                [62 ]Genome Institute of Singapore, A*STAR , Singapore
                [63 ]Georg-Speyer-Haus Institute for Tumor Biology and Experimental Therapy , Frankfurt, Germany
                [64 ]George Papanicolaou Hospital, Public Cord Blood Bank, Department of Haematology - BMT Unit , Thessaloniki, Greece
                [65 ]Georgetown University, Department of Medicine , Washington, DC, USA
                [66 ]German Armed Forces Central Hospital, Department of General, Visceral and Thoracic Surgery , Koblenz, Germany
                [67 ]German Cancer Consortium (DKTK), Partner Site Freiburg and German Cancer Research Center (DKFZ) , Heidelberg, Germany
                [68 ]German Cancer Research Center (DKFZ), Clinical Cooperation Unit Applied Tumor Biology , Heidelberg, Germany
                [69 ]German Cancer Research Center (DKFZ), Division Signaling and Functional Genomics , Heidelberg, Germany
                [70 ]German Centre for Neurodegenerative Diseases (DZNE) , Bonn, Germany
                [71 ]German Research Center for Environmental Health, Institute for Virology , Munich, Germany
                [72 ]Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, REMAR-IVECAT Group , Badalona, Spain
                [73 ]Germans Trias i Pujol University Hospital, Nephrology Service , Badalona, Spain
                [74 ]Ghent University Hospital, Department of Urology , Ghent, Belgium
                [75 ]Ghent University, Department of Radiation Oncology and Experimental Cancer Research, Laboratory of Experimental Cancer Research , Ghent, Belgium
                [76 ]Graduate School of Public Health at the University of Pittsburgh, Division of Occupational and Environmental Medicine , Pittsburgh, PA, USA
                [77 ]Guangzhou Medical University, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Key Laboratory of Molecular Target & Clinical Pharmacology , Guangzhou, China
                [78 ]Haaglanden Medical Center, Department of Neurosurgery , The Hague, The Netherlands
                [79 ]Harvard Medical School, Cardiovascular Medicine , Boston, MA, USA
                [80 ]Harvard Medical School, Department of Medicine , Boston, MA, USA
                [81 ]Harvard University, Harvard T.H. Chan School of Public Health , Boston, MA, USA
                [82 ]Harvard University, School of Engineering and Applied Sciences , Cambridge, MA, USA
                [83 ]Hasselt University, Biomedical Research Institute (BIOMED), Department of Medicine and Life Sciences , Hasselt, Belgium
                [84 ]Hasselt University, Biomedical Research Institute (BIOMED) , Hasselt, Belgium
                [85 ]Helmholtz Center Munich German Research Center for Environmental Health, Research Unit Gene Vectors , Munich, Germany
                [86 ]Helmholtz-Centre for Infection Research , Braunschweig, Germany
                [87 ]Helmholtz-Institute for Pharmaceutical Research Saarland , Saarbrücken, Germany
                [88 ]Hiroshima University, Institute of Biomedical & Health Sciences, Department of Cellular and Molecular Biology , Hiroshima, Japan
                [89 ]Houston Methodist Research Institute, Department of Nanomedicine , Houston, TX, USA
                [90 ]Hudson Institute of Medical Research , Melbourne, Australia
                [91 ]Icahn School of Medicine at Mount Sinai, Department of Medicine, Cardiology , New York City, NY, USA
                [92 ]Icahn School of Medicine at Mount Sinai , New York City, NY, USA
                [93 ]IIS-Fundacion Jimenez Diaz-UAM, Department of Nephrology and Hypertension , Madrid, Spain
                [94 ]IKERBASQUE Research Science Foundation , Bilbao, Spain
                [95 ]Imperial College London , London, UK
                [96 ]INEB - Instituto de Engenharia Biomédica , Porto, Portugal
                [97 ]INSERM U1063, Université d’Angers, CHU d’Angers , Angers, France
                [98 ]INSERM U1068, Aix Marseille University, CNRS UMR7258 , Marseille, France
                [99 ]INSERM U1110 , Strasbourg, France
                [100 ]INSERM UMR-S 970, Paris Cardiovascular Research Center , Paris, France
                [101 ]Institució Catalana de Recerca i Estudis Avançats (ICREA) , Barcelona, Spain
                [102 ]Institut Curie, CNRS UMR144, PSL Research University , Paris, France
                [103 ]Institut Curie, INSERM U932, PSL Research University , Paris, France
                [104 ]Institut d’Investigació Germans Trias i Pujol (IGTP), PVREX group , Badalona, Spain
                [105 ]Institut Pasteur de Montevideo, Functional Genomics Unit , Montevideo, Uruguay
                [106 ]Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council (CNR) of Italy , Palermo, Italy
                [107 ]Institute of Medical Biology (IMB), Agency for Science and Technology (A*STAR) , Singapore
                [108 ]Institute of Physiology CAS, Department of Biomaterials and Tissue Engineering, BIOCEV , Vestec, Czech Republic
                [109 ]Institute of Physiology CAS, Department of Biomaterials and Tissue Engineering , Prague, Czech Republic
                [110 ]Instituto Oswaldo Cruz , Rio de Janeiro, Brazil
                [111 ]INSTM - National Interuniversity Consortium of Materials Science and Technology , Florence, Italy
                [112 ]Interuniversity Research Institute for Molecular Recognition and Technological Development (IDM), University of Valencia, Polytechnic University of Valencia , Valencia, Spain
                [113 ]IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto , Porto, Portugal
                [114 ]IRCCS - Istituto Ortopedico Rizzoli, Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine , Bologna, Italy
                [115 ]IRCCS Fondazione Don Carlo Gnocchi, Laboratory of Nanomedicine and Clinical Biophotonics (LABION) , Milan, Italy
                [116 ]IRCCS MultiMedica , Milan, Italy
                [117 ]ISGlobal, Hospital Clínic - Universitat de Barcelona, PVREX Group , Barcelona, Spain
                [118 ]Istanbul University Oncology Institute, Basic Oncology Department , Istanbul, Turkey
                [119 ]Jagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology, Department of Cell Biology , Kraków, Poland
                [120 ]James Cook University, Australian Institute of Tropical Health and Medicine, Centre for Biodiscovery and Molecular Development of Therapeutics , Cairns, Australia
                [121 ]K.G. Jebsen Brain Tumor Research Centre, Department of Biomedicine, University of Bergen , Bergen, Norway
                [122 ]Kansas State University, College of Veterinary Medicine , Manhattan, KS, USA
                [123 ]Karolinska Institute, Clinical Research Center, Department of Laboratory Medicine , Stockholm, Sweden
                [124 ]Karolinska Institute, Clinical Research Center, Unit for Molecular Cell and Gene Therapy Science , Stockholm, Sweden
                [125 ]Karolinska Institute, Department of Medicine and Center for Molecular Medicine, Respiratory Medicine Unit , Stockholm, Sweden
                [126 ]Karolinska Institute, Department of Medicine Solna, Division for Immunology and Allergy , Stockholm, Sweden
                [127 ]Karolinska Institute , Stockholm, Sweden
                [128 ]Kidney Research Centre , Ottawa, Canada
                [129 ]KU Leuven (Leuven University), Department of Human Genetics , Leuven, Belgium
                [130 ]Kyung Hee University, Department of Applied Chemistry , Yongin, Korea
                [131 ]La Trobe University, La Trobe Institute for Molecular Science, Department of Biochemistry and Genetics , Bundoora, Australia
                [132 ]Latvian Biomedical Research and Study Centre , Riga, Latvia
                [133 ]Leibniz Institute for Farm Animal Biology (FBN), Institute of Reproductive Biology , Dummerstorf, Germany
                [134 ]Leiden University Medical Center, Department of Neurosurgery , Leiden, The Netherlands
                [135 ]Loyola University Chicago, Department of Urology , Maywood, IL, USA
                [136 ]Lund University, Department of Cardiology , Lund, Sweden
                [137 ]Maastricht University, GROW, School for Oncology and Developmental Biology, Maastricht Radiation Oncology (MaastRO) Lab , Maastricht, The Netherlands
                [138 ]Maria Sklodowska-Curie Institute - Oncology Center, Gliwice Branch , Gliwice, Poland
                [139 ]Massachusetts General Cancer Center , Boston, MA, USA
                [140 ]Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Department of Neurology and Radiology , Boston, MA, USA
                [141 ]Massachusetts General Hospital , Boston, MA, USA
                [142 ]Massachusetts General Hospital, Department of Neurology , Boston, MA, USA
                [143 ]Massachusetts General Hospital, Department of Neurosurgery , Boston, MA, USA
                [144 ]Massachusetts General Hospital, Harvard Medical School, Department of Neurology , Boston, MA, USA
                [145 ]Mayo Clinic, College of Medicine, Department of Physiology and Biomedical Engineering , Rochester, MN, USA
                [146 ]Mayo Clinic, Department of Orthopedic Surgery , Rochester, MN, USA
                [147 ]Mayo Clinic, Department of Transplantation Medicine/Department of Physiology and Biomedical Engineering , Jacksonville, FL, USA
                [148 ]Mayo Clinic, Department of Transplantation , Jacksonville, FL, USA
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                [153 ]McGill University, The Research Institute of the McGill University Health Centre , Montreal, Canada
                [154 ]Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Institute for Infection Prevention and Hospital Epidemiology , Freiburg, Germany
                [155 ]Memorial Sloan Kettering Cancer Center, Department of Medicine , New York City, NY, USA
                [156 ]Monash University , Melbourne, Australia
                [157 ]Mossakowski Medical Research Centre, NeuroRepair Department , Warsaw, Poland
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                [159 ]MRC The Gambia , Fajara, The Gambia
                [160 ]MTA-SE Immuno-Proteogenomics Research Groups , Budapest, Hungary
                [161 ]Namur Thrombosis and Hemostasis Center (NTHC), NARILIS , Namur, Belgium
                [162 ]Nanfang Hospital, Southern Medical University, Department of Clinical Laboratory Medicine , Guangzhou, China
                [163 ]National Cancer Center Research Institute, Division of Molecular and Cellular Medicine , Tokyo, Japan
                [164 ]National Cancer Center Research Institute , Tokyo, Japan
                [165 ]National Institute of Chemistry, Department of Molecular Biology and Nanobiotechnology , Ljubljana, Slovenia
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                [177 ]Oslo University Hospital-The Norwegian Radium Hospital, Institute for Cancer Research, Department of Molecular Cell Biology , Oslo, Norway
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                [180 ]Ottawa Hospital Research Institute , Ottawa, Canada
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                [184 ]Philipps University Marburg, Experimental Tumor Biology , Marburg, Germany
                [185 ]Pontificia Universidad Católica de Chile, Advanced Center for Chronic Diseases (ACCDiS) , Santiago, Chile
                [186 ]Pontificia Universidad Católica de Chile, Faculty of Medicine, Department of Hematology-Oncology , Santiago, Chile
                [187 ]POSTECH (Pohang University of Science and Technology), Department of Life Sciences , Pohang, South Korea
                [188 ]Princess Margaret Cancer Centre, University Health Network , Toronto, Canada
                [189 ]QIMR Berghofer Medical Research Institute , Herston, Australia
                [190 ]Queen Mary University of London, Blizard Institute, Epigenetics & Cellular Senescence Group , London, UK
                [191 ]Radboud University Medical Center, Department of Rheumatology , Nijmegen, The Netherlands
                [192 ]Regional Research Network on Extracellular Vesicles, RRNEV , Oslo, Norway
                [193 ]René Rachou Institute/FIOCRUZ , Belo Horizonte, Brazil
                [194 ]Research Service, Olin E. Teague Veterans’ Medical Center , Temple, TX, USA
                [195 ]Royan Institute for Stem Cell Biology and Technology, ACECR, Cell Science Research Center, Department of Stem Cells and Developmental Biology , Tehran, Iran
                [196 ]Saarland University Medical Center, Department of Medicine II , Homburg, Germany
                [197 ]Saarland University , Saarbrücken, Germany
                [198 ]Sanjay Gandhi Postgraduate Institute of Medical Sciences, Department of Molecular Medicine & Biotechnology , Lucknow, India
                [199 ]Sapienza University of Rome, Department of Experimental Medicine , Rome, Italy
                [200 ]Scintillon Institute , La Jolla, CA, USA
                [201 ]Semmelweis University, Department of Genetics, Cell- and Immunobiology , Budapest, Hungary
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                [209 ]Statens Serum Institut, Department of Autoimmunology and Biomarkers , Copenhagen, Denmark
                [210 ]Stellenbosch University, Department of Physiological Sciences , Stellenbosch, South Africa
                [211 ]Technical University Eindhoven, Faculty Biomedical Technology , Eindhoven, The Netherlands
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                [213 ]Technische Universität Darmstadt, Department of Biology , Darmstadt, Germany
                [214 ]Texas A&M University College of Medicine, Institute for Regenerative Medicine and Department of Molecular and Cellular Medicine , College Station, TX, USA
                [215 ]TGen, Neurogenomics Division , Phoenix, AZ, USA
                [216 ]The Florey Institute of Neuroscience and Mental Health , Melbourne, Australia
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                [218 ]The Johns Hopkins University School of Medicine, Department of Neurology , Baltimore, MD, USA
                [219 ]The Johns Hopkins University School of Medicine, Department of Psychiatry and Behavioral Sciences , Baltimore, MD, USA
                [220 ]The Ohio State University, College of Pharmacy, Division of Pharmaceutics and Pharmaceutical Chemistry , Columbus, OH, USA
                [221 ]The Ohio State University , Columbus, OH, USA
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                [223 ]The School of Biomedical Sciences, University of Western Australia , Perth, Australia
                [224 ]The Scripps Research Institute-Scripps Florida, Department of Molecular Medicine , Jupiter, FL, USA
                [225 ]The Sociedade Beneficente Israelita Brasileira Albert Einstein , São Paulo, Brazil
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                [229 ]The University of Sheffield , Sheffield, UK
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                [236 ]Tsinghua University, School of Pharmaceutical Sciences , Beijing, China
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                [249 ]Università degli Studi di Milano, Department of Clinical Sciences and Community Health, EPIGET LAB , Milan, Italy
                [250 ]Universitat Autònoma de Barcelona, Department of Cell Biology, Physiology & Immunology , Barcelona, Spain
                [251 ]Universitat Autònoma de Barcelona, Hospital Universitari and Health Sciences Research Institute Germans Trias i Pujol, Department of Pathology , Barcelona, Spain
                [252 ]Universitat de València, Departament de Farmàcia i Tecnologia Farmacèutica i Parasitologia, Àrea de Parasitologia , Valencia, Spain
                [253 ]Universitat de València, Health Research Institute La Fe, Joint Research Unit on Endocrinology, Nutrition and Clinical Dietetics , Valencia, Spain
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                [255 ]Université Catholique de Louvain, CHU UCL Namur, Hematology-Hemostasis Laboratory , Yvoir, Belgium
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                [259 ]Université de Strasbourg , Strasbourg, France
                [260 ]Université Laval, Centre de Recherche du CHU de Québec, Department of Infectious Diseases and Immunity , Quebec City, Canada
                [261 ]Université Paris Descartes, Sorbonne Paris Cité , Paris, France
                [262 ]Universiteit Hasselt , Diepenbeek, Belgium
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                [264 ]University College London , London, UK
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                [268 ]University Hospital RWTH Aachen, Department of Thoracic and Cardiovascular Surgery , Aachen, Germany
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                [283 ]University of Brescia, Department of Molecular and Translational Medicine , Brescia, Italy
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                [286 ]University of Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS) , Buenos Aires, Argentina
                [287 ]University of California, Davis, Department of Nutrition , Davis, CA, USA
                [288 ]University of California, Davis, Department of Otolaryngology , Davis, CA, USA
                [289 ]University of California, Los Angeles, California NanoSystems Institute , Los Angeles, CA, USA
                [290 ]University of California, Los Angeles, Department of Bioengineering , Los Angeles, CA, USA
                [291 ]University of California, Los Angeles, Department of Pathology and Laboratory Medicine , Los Angeles, CA, USA
                [292 ]University of California, Los Angeles, Jonsson Comprehensive Cancer Center , Los Angeles, CA, USA
                [293 ]University of California, San Diego, Department of Neurosurgery , La Jolla, CA, USA
                [294 ]University of California, San Diego, Department of Obstetrics, Gynecology, and Reproductive Sciences , La Jolla, CA, USA
                [295 ]University of California, San Diego, Department of Pediatrics , San Diego, CA, USA
                [296 ]University of California , San Francisco, CA, USA
                [297 ]University of Cambridge School of Clinical Medicine, Addenbrooke’s Hospital, Department of Medicine, Cambridge NIHR BRC Cell Phenotyping Hub , Cambridge, UK
                [298 ]University of Campinas, Piracicaba Dental School, Department of Oral Diagnosis , Piracicaba, Brazil
                [299 ]University of Chile, Faculty of Chemical and Pharmaceutical Science, Laboratory of Nanobiotechnology and Nanotoxicology , Santiago, Chile
                [300 ]University of Cincinnati College of Medicine , Cincinnati, OH, USA
                [301 ]University of Cologne, Department of Internal Medicine I , Cologne, Germany
                [302 ]University of Colorado, School of Medicine, Department of Ophthalmology, Cell Sight-Ocular Stem Cell and Regeneration Program , Aurora, CO, USA
                [303 ]University of Copenhagen, Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Protein Research , Copenhagen, Denmark
                [304 ]University of Copenhagen, Institute of Clinical Medicine , Copenhagen, Denmark
                [305 ]University of Edinburgh, Institute of Immunology & Infection Research , Edinburgh, UK
                [306 ]University of Gothenburg, Institute of Clinical Sciences at Sahlgrenska Academy, Department of Biomaterials , Gothenburg, Sweden
                [307 ]University of Gothenburg, Institute of Clinical Sciences, Department of Surgery, Sahlgrenska Cancer Center , Gothenburg, Sweden
                [308 ]University of Gothenburg, Institute of Medicine at Sahlgrenska Academy, Krefting Research Centre , Gothenburg, Sweden
                [309 ]University of Gothenburg, Sahlgrenska Academy, Department of Rheumatology and Inflammation Research , Gothenburg, Sweden
                [310 ]University of Gothenburg, The Sahlgrenska Academy, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry , Mölndal, Sweden
                [311 ]University of Helsinki, EV Core Facility , Helsinki, Finland
                [312 ]University of Helsinki, Faculty of Biological and Environmental Sciences, Molecular and Integrative Biosciences Research Programme, EV group , Helsinki, Finland
                [313 ]University of Hertfordshire, School of Life and Medical Sciences, Biosciences Research Group , Hatfield, UK
                [314 ]University of Kentucky, College of Medicine, Department of Physiology , Lexington, KY, USA
                [315 ]University of L’Aquila, Department of Life, Health and Environmental Sciences , L’Aquila, Italy
                [316 ]University of Liège, GIGA-R(MBD), PSI Laboratory , Liège, Belgium
                [317 ]University of Ljubljana, Faculty of Medicine, Institute of Biochemistry , Ljubljana, Slovenia
                [318 ]University of Lyon, INRA, EPHE, UMR754 Viral Infections and Comparative Pathology , Lyon, France
                [319 ]University of Lyon, Lyon-Sud Faculty of Medicine, CarMeN Laboratory (UMR INSERM 1060-INRA 1397) , Pierre-Bénite, France
                [320 ]University of Mainz, Institute of Developmental Biology and Neurobiology , Mainz, Germany
                [321 ]University of Malta, Department of Pathology , Msida, Malta
                [322 ]University of Manchester, Division of Cancer Sciences, Manchester Cancer Research Centre , Manchester, UK
                [323 ]University of Manchester , Manchester, UK
                [324 ]University of Maryland, Fischell Department of Bioengineering , College Park, MD, USA
                [325 ]University of Massachusetts Medical School, RNA Therapeutics Institute , Worcester, MA, USA
                [326 ]University of Michigan Medical School , Ann Arbor, MI, USA
                [327 ]University of Michigan, Biointerfaces Institute , Ann Arbor, MI, USA
                [328 ]University of Michigan, Department of Biomedical Engineering , Ann Arbor, MI, USA
                [329 ]University of Michigan, Department of Internal Medicine - Hematology/Oncology Division , Ann Arbor, MI, USA
                [330 ]University of Michigan, Department of Medicine , Ann Arbor, MI, USA
                [331 ]University of Michigan, Department of Urology , Ann Arbor, MI, USA
                [332 ]University of Minnesota Medical School, Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics , Minneapolis, MN, USA
                [333 ]University of Modena and Reggio Emilia, Division of Oncology , Modena, Italy
                [334 ]University of Nebraska Medical Center, Department of Pharmacology and Experimental Neuroscience , Omaha, NE, USA
                [335 ]University of Notre Dame, Department of Biological Sciences , Notre Dame, IN, USA
                [336 ]University of Oslo, Institute of Clinical Medicine , Oslo, Norway
                [337 ]University of Ottawa , Ottawa, Canada
                [338 ]University of Oulu, Faculty of Medicine, Cancer and Translational Medicine Research Unit , Oulu, Finland
                [339 ]University of Oxford, Department of Physiology, Anatomy and Genetics , Oxford, UK
                [340 ]University of Oxford, Radcliffe Department of Medicine, Acute Stroke Programme - Investigative Medicine , Oxford, UK
                [341 ]University of Padova, Department of Comparative Biomedicine and Food Science , Padova, Italy
                [342 ]University of Padova, Department of Women’s and Children’s Health , Padova, Italy
                [343 ]University of Palermo, Department of Biopathology and Medical Biotechnologies , Palermo, Italy
                [344 ]University of Perugia, Department of Chemistry, Biology and Biotechnology , Perugia, Italy
                [345 ]University of Pisa, Centro Dipartimentale di Biologia Cellulare Cardio-Respiratoria , Pisa, Italy
                [346 ]University of Porto, Faculty of Pharmacy (FFUP), IBMC/I3S , Porto, Portugal
                [347 ]University of Porto, Faculty of Pharmacy (FFUP) , Porto, Portugal
                [348 ]University of Porto, i3S-Instituto de Investigação e Inovação em Saúde , Porto, Portugal
                [349 ]University of Porto, ICBAS - Instituto de Ciências Biomédicas Abel Salazar , Porto, Portugal
                [350 ]University of Rochester , Rochester, NY, USA
                [351 ]University of São Paulo, Ribeirão Preto Medical School, Department of Pathology and Forensic Medicine , Ribeirão Preto, Brazil
                [352 ]University of São Paulo, Ribeirão Preto Medical School , Ribeirão Preto, Brazil
                [353 ]University of Science and Culture, ACECR, Department of Developmental Biology , Tehran, Iran
                [354 ]University of South Alabama, Department of Pharmacology, Center for Lung Biology , Mobile, AL, USA
                [355 ]University of Southern California Keck School of Medicine , Los Angeles, CA, USA
                [356 ]University of Southern California , Los Angeles, CA, USA
                [357 ]University of Technology Sydney, Discipline of Pharmacy, Graduate School of Health , Sydney, Australia
                [358 ]University of Texas MD Anderson Cancer Center, Department of Cancer Biology, Metastasis Research Center , Houston, TX, USA
                [359 ]University of Torino, Department of Medical Sciences , Torino, Italy
                [360 ]University of Torino, Department of Molecular Biotechnology and Health Sciences , Torino, Italy
                [361 ]University of Toronto, Department of Anesthesia , Toronto, Canada
                [362 ]University of Toronto, Department of Laboratory Medicine and Pathobiology , Toronto, Canada
                [363 ]University of Toronto, Department of Medical Biophysics , Toronto, Canada
                [364 ]University of Toronto, Department of Medicine, Division of Neurology , Toronto, Canada
                [365 ]University of Tsukuba , Tsukuba, Japan
                [366 ]University of Virginia Health System, Department of Medicine, Division of Nephrology , Charlottesville, VA, USA
                [367 ]University of Virginia, Flow Cytometry Core, School of Medicine , Charlottesville, VA, USA
                [368 ]University of Würzburg, Rudolf Virchow Center , Würzburg, Germany
                [369 ]Utrecht University, Faculty of Veterinary Medicine, Department of Biochemistry and Cell Biology , Utrecht, The Netherlands
                [370 ]Utrecht University, University Medical Center Utrecht, Center for Molecular Medicine & Regenerative Medicine Center , Utrecht, The Netherlands
                [371 ]Utrecht University, University Medical Center Utrecht, Department of Neurosurgery, Brain Center Rudolf Magnus, Institute of Neurosciences , Utrecht, The Netherlands
                [372 ]Utrecht University, University Medical Center Utrecht, Department of Pathology , Utrecht, The Netherlands
                [373 ]Vanderbilt University Medical Center, Epithelial Biology Center, Department of Medicine , Nashville, TN, USA
                [374 ]Vanderbilt University School of Medicine, Department of Cell and Developmental Biology , Nashville, TN, USA
                [375 ]Veterans Affairs Medical Center , San Francisco, CA, USA
                [376 ]Vilnius University, Institute of Biomedical Sciences, Department of Physiology, Biochemistry, Microbiology and Laboratory Medicine , Vilnius, Lithuania
                [377 ]Vlaamse Instelling voor Technologisch Onderzoek (VITO) , Mol, Belgium
                [378 ]Washington University , Saint Louis, MO, USA
                [379 ]Weill Cornell Medicine, Department of Medicine , New York City, NY, USA
                [380 ]Weizmann Institute of Science, Department of Biomolecular Sciences , Rehovot, Israel
                [381 ]West Virginia University, Department of Chemical and Biomedical Engineering and WVU Cancer Institute , Morgantown, WV, USA
                [382 ]West Virginia University, Department of Microbiology Immunology and Cell Biology , Morgantown, WV, USA
                [383 ]West Virginia University , Morgantown, WV, USA
                [384 ]Xiamen University, Department of Chemical Biology , Xiamen, China
                Author notes
                CONTACT Clotilde Théry Clotilde.Thery@ 123456curie.fr Institut Curie/INSERM U932, 26 rue d’Ulm, 75005Paris, France
                Kenneth W Witwer kwitwer1@ 123456jhmi.edu 733 North Broadway, MRB 829 Baltimore, MD21205, USA
                [*]

                These authors are co-corresponding authors and contributed equally to this work. All authors, except for the corresponding authors, are listed alphabetically.

                This article was first drafted begining in late 2017 and finalized in September, 2018 with several rounds of feedback from the ISEV Executive Board and JEV Editorial Board.

                [&]

                The following authors are members of the 2016-2018 and/or 2018-2020 ISEV Board of Directors: Cherie Blenkiron, Edit I Buzas, Dolores Di Vizio, Uta Erdbrügger, Juan M Falcón-Pérez, Chris Gardiner, Andrew F Hill (current President), Raghu Kalluri, Jan Lötvall (past President), Malene Møller Jørgensen, Rienk Nieuwland, Lorraine O’Driscoll, Susmita Sahoo, Carolina Soekmadji, Hidetoshi Tahara, Ana Claudia Torrecilhas, Marca HM Wauben, Alissa Weaver, Kenneth W Witwer, Hang (Hubert) Yin, Lei Zheng.

                [£]

                The following authors are Editors of the Journal of Extracellular Vesicles: Editors-in-Chief: Clotilde Théry, Peter Quesenberry, Yong Song Gho; Associate Editors: Elena Aikawa, Chantal Boulanger, Edit I Buzas, Giovanni Camussi, Emanuele Cocucci, Dolores Di Vizio, Andrew F Hill, Harry Holthofer, Kwang Pyo Kim, Eva-Maria Krämer-Albers, Saara Laitinen, Cecilia Lässer, Suresh Mathivanan, Esther Nolte-’t Hoen, Takahiro Ochiya, Hector Peinado, Janusz Rak, Neta Regev-Rudzki, Raymond Schiffelers, Marca HM Wauben, Kenneth W Witwer.

                [#]

                Authors who are members of the International Society for Cell and Gene Therapy (ISCT) Exosomes Scientific Committee include Sai Kiang Lim (Co-Chair), Bernd Giebel (Co-Chair), Luis A Ortiz, Donald G Phinney and Daniel J Weiss (ISCT Chief Scientific Officer). Massimo Dominici is Past President of ISCT.

                [$]

                Authors who are members of the joined ISEV-ISAC (International Society for Advancement of Cytometry)-ISTH (International Society on Thrombosis and Haemostasis) EV Flow Cytometry Working group are: Alain Brisson, Frank AW Coumans, André Görgens, Jennifer C Jones, Joanne Lannigan, Sten Libregts, François Mullier, Rienk Nieuwland, John P Nolan, Marca HM Wauben, Joshua A Welsh.

                Author information
                http://orcid.org/0000-0001-8294-6884
                http://orcid.org/0000-0003-1664-4233
                Article
                1535750
                10.1080/20013078.2018.1535750
                6322352
                30637094
                5b60b780-768f-4334-9573-22d3c3f9dd43
                © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 September 2018
                : 25 September 2018
                Page count
                Tables: 4, References: 320, Pages: 44
                Funding
                Funded by: Agence Nationale de la Recherche 10.13039/501100001665
                Award ID: ANR-11-LABX-0043
                Funded by: Agence Nationale de la Recherche 10.13039/501100001665
                Award ID: ANR-10-IDEX-0001-02 PSL
                Funded by: National Institute on Aging 10.13039/100000049
                Award ID: AG057430
                Funded by: National Institute on Drug Abuse 10.13039/100000026
                Award ID: DA040385
                Funded by: INSERM, Institut Curie, Ministry of Education
                Award ID: NA
                Funded by: INCa
                Award ID: INCA-11548
                Funded by: Fondation ARC
                Award ID: PGA1 RF20180206962
                Funded by: Fondation ARC
                Award ID: PJA 20171206453
                Funded by: Sidaction 10.13039/100009060
                Award ID: 17-1-AAE-1138
                Funding is listed only for the corresponding authors. CT’s laboratory is funded by INSERM, Institut Curie, Ministry of Education, and grants from INCa (INCA-11548), French National Research Agency (ANR-10-IDEX-0001-02 PSL* and ANR-11-LABX-0043), SIDACTION (17-1-AAE-1138), Fondation ARC (PGA1 RF20180206962, PJA 20171206453). KWW and CT receive support from NIDA (DA040385). KWW is also supported in part by NIA AG057430, NIDA DA047807 and NIMH MH118164.
                Categories
                Position Paper

                extracellular vesicles,exosomes,ectosomes,microvesicles,minimal information requirements,guidelines,standardization,microparticles,rigor,reproducibility

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